What is primary aldosteronism?

What is Primary Aldosteronism

Primary aldosteronism is a condition characterized by excessive and autonomous production of aldosterone by the adrenal glands, independent of the renin-angiotensin system, making it the most common cause of secondary hypertension and a potentially curable form of high blood pressure. 1, 2

Core Pathophysiology

• Aldosterone is produced autonomously by the adrenal glands in amounts that cannot be suppressed by sodium loading, distinguishing it from normal physiologic aldosterone secretion 1
• This excessive aldosterone causes sodium retention, suppression of plasma renin activity, and increased potassium excretion through the distal renal tubules 2, 3
• Hypokalemia occurs in only approximately 50% of cases, so normal potassium levels do not exclude the diagnosis 1, 4

Major Subtypes

• Unilateral disease (≈50% of cases): Usually caused by an aldosterone-producing adenoma or rarely unilateral adrenal hyperplasia 2, 5
• Bilateral disease (≈50% of cases): Caused by bilateral adrenal hyperplasia, also called idiopathic hyperaldosteronism 2, 5
• Rare familial forms: Caused by germline mutations (familial hyperaldosteronism types 1-4) 5, 6

Clinical Prevalence and Significance

• Primary aldosteronism affects 5-10% of all hypertensive patients and up to 20% of patients with resistant hypertension 1, 3
• Despite being common, only approximately 2-4% of eligible patients are actually screened and diagnosed 1, 4

Cardiovascular Impact Beyond Blood Pressure

Primary aldosteronism causes dramatically worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels 1:

• 12.1-fold increased risk of atrial fibrillation 1

• 6.5-fold increased risk of myocardial infarction 1

• 4.2-fold increased risk of stroke 1, 3

• 3.7-fold increased risk of heart failure 1

• Aldosterone exerts direct toxic effects on cardiovascular and renal tissues, causing widespread fibrosis, left ventricular hypertrophy, arterial stiffness, and kidney damage independent of blood pressure elevation 2, 3

Genetic Basis

• Somatic mutations in genes including KCNJ5, CACNA1D, ATP1A1, ATP2B3, and CTNNB1 drive autonomous aldosterone production in most adenomas 5, 6
• Aldosterone-producing cell clusters beneath the adrenal capsule accumulate with age and harbor similar mutations, suggesting they may be precursors to adenomas 6
• Rare germline variants cause familial forms of hyperaldosteronism 6

Treatment Implications

• For unilateral disease: Laparoscopic unilateral adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and curing hypertension in approximately 50% 1, 2
• For bilateral disease: Lifelong medical therapy with mineralocorticoid receptor antagonists (spironolactone or eplerenone) is the cornerstone of treatment 1, 2
• The deleterious effects of aldosterone excess are often reversible with appropriate treatment, reducing cardiovascular events and improving cardiac and kidney function 2, 3

Why Early Diagnosis Matters

• Targeted treatment (surgery or mineralocorticoid receptor antagonists) can reverse aldosterone-mediated target organ damage and mitigate excess cardiovascular risk 1, 5
• The rate of cure is higher when diagnosis is made early in the disease course, before irreversible vascular remodeling occurs 1
• Primary aldosteronism represents a potentially curable cause of hypertension that, if left untreated, carries substantially higher morbidity and mortality than essential hypertension 7, 8